Angiogenesis, the process of forming new blood vessels, is critical in many normal and abnormal physiological states. Under normal physiological conditions, humans or animals undergo angiogenesis in specific and restricted situations. For example, angiogenesis is normally observed in wound healing, fetal and embryonic development and formation of the corpus luteum, endometrium and placenta.
Undesirable or inappropriately regulated angiogenesis occurs in a many disorders, in which abnormal endothelial growth may cause or participate in the pathological process. For example, abnormal endothelial cell proliferation has been postulated to contribute to atherosclerosis. Angiogenesis also participates in the growth of many tumors. Deregulated angiogenesis has been implicated in pathological processes such as rheumatoid arthritis, retinopathies, hemangiomas, and psoriasis. The diverse pathological disease states in which unregulated angiogenesis is present have been categorized as angiogenesis-dependent or angiogenesis-associated diseases.
Inadequate angiogenesis is implicated in several diseases and biological processes. Inadequate vascularization of the uterine endometrium and associated infertility, wound repair, healing of cuts and incisions, are some of the examples of problems caused by or associated with inadequate angiogenesis.
Both controlled and uncontrolled angiogenesis are thought to proceed in a similar manner. Endothelial cells and pericytes, surrounded by a basement membrane, form capillary blood vessels. Angiogenesis begins with the erosion of the basement membrane by enzymes released by endothelial cells and leukocytes. The endothelial cells, which line the lumen of blood vessels, then protrude through the basement membrane. Angiogenic stimulants induce the endothelial cells to migrate through the eroded basement membrane. The migrating cells form a “sprout” protruding from the parent blood vessel, where the endothelial cells undergo mitosis and proliferate. Endothelial sprouts merge with each other to form capillary loops, creating the new blood vessel.
What is needed therefore are compositions and methods which can modulate angiogenesis according to specific situations. These include methods and compositions which can inhibit the unwanted growth of blood vessels, especially the newly formed blood vessels that support tumor growth. Furthermore, it is also desirable to have methods and compositions which can promote angiogenesis to treat inadequate angiogenesis in certain diseases and processes.